The US Food and Drug Administration (FDA) scientists have presented their analysis of publicly available whole-genome sequencing data from genome-edited cattle. The analysis presents evidence of unintended alterations at a genome-edited target site (Norris et al., (2020) Nat. Biotechnol.38, 163–164, https://www.nature.com/articles/s41587-019-0394-6). The intended genome edit sought to introduce the Celtic POLLED allele into Holstein cattle. This allele exists in some other cattle breeds and results in the animals lacking horns (or being ‘polled’). As sometimes occurs with germline genomic alterations, however, the editing also produced unintended alterations which resulted in the integration of a bacterial plasmid containing various sequences designed for use in molecular biology, including antibiotic resistance markers.

The FDA cites this analysis to show why it is necessary for there to be regulatory oversight of intentional genomic alterations in animals, even when the intended modification seeks to replicate a naturally occurring mutation (Solomon (2020). ‘Genome Editing in Animals: Why FDA Regulation Matters’. Nat. Biotechnol. 38, 142–143, https://www.nature.com/articles/s41587-020-0413-7). The analysis demonstrates that genome editing in animals can have unintended consequences and that regulators must be alert to the possibility of such consequences. There is good reason for regulators to analyze data on intentional genomic alterations in animals to determine whether there are any unintended results, either on- or off-target and, if so, to determine whether they present any cause for regulatory concern. Unintended alterations can have unexpected and deleterious consequences no matter the size of the alteration or how it was produced.

The FDA emphasizes that it wants to know that an intentional genomic alteration in animals will not inadvertently produce such results. The FDA also wants to ensure these alterations do not affect food safety. It cautions that unintended alterations may affect protein expression, including the disruption of protein function, changes to the expression level of a protein (such as the overexpression of a hormone receptor), or the creation of a new expression product.